Chimerin 1

Search for
Structures	Swiss-model
Domains	InterPro

chimerin (chimaerin) 1
chimerin (chimaerin) 1
	Crystal structure of human chimerin 1 (CHN1)
Identifiers
Symbol	CHN1
Alt. symbols	CHN
NCBI gene	1123
HGNC	1943
OMIM	118423
RefSeq	NM_001822
UniProt	P15882
Other data
Locus	Chr. 2 q31-q32.1
Structures
Search for
Structures	Swiss-model
Domains	InterPro

CHN1
Identifiers
Aliases	CHN1, chimerin 1, ARHGAP2, CHN, DURS2, NC, RHOGAP2
External IDs	OMIM: 118423; MGI: 1915674; GeneCards: CHN1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2OSA, 3CXL
Gene location (Human)
Chr.	Chromosome 2 (human)
End	175,005,381 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	73,775,346 bp
RNA expression pattern
	Top expressed in
	middle temporal gyrus; ; Brodmann area 23; ; endothelial cell; ; primary visual cortex; ; superior frontal gyrus; ; orbitofrontal cortex; ; frontal pole; ; Brodmann area 46; ; dorsolateral prefrontal cortex; ; parietal lobe;
	Top expressed in
	dentate gyrus of hippocampal formation granule cell; ; superior frontal gyrus; ; olfactory tubercle; ; primary motor cortex; ; primary visual cortex; ; amygdala; ; piriform cortex; ; prefrontal cortex; ; subdivision of hippocampus; ; hippocampus proper;
	More reference expression data
	n/a
Gene ontology
Molecular function	ephrin receptor binding; protein binding; metal ion binding; GTPase activator activity;
Cellular component	cytoplasm; cytosol;
Biological process	regulation of axonogenesis; positive regulation of GTPase activity; intracellular signal transduction; motor neuron axon guidance; regulation of small GTPase mediated signal transduction; nervous system development; signal transduction; positive regulation of signal transduction; ephrin receptor signaling pathway; regulation of GTPase activity;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	1123
	108699
	ENSG00000128656
	ENSMUSG00000056486
	P15882
	Q91V57
	NM_001025201; NM_001206602; NM_001822; NM_001371513; NM_001371514
	NM_001113246; NM_001166603; NM_001166604; NM_029716; NM_175752
	NP_001020372; NP_001193531; NP_001813
	NP_001106717; NP_001160075; NP_001160076; NP_083992; NP_786928
	Wikidata
View/Edit Human	View/Edit Mouse

Chimerin 1 (CHN1), also known as alpha-1-chimerin, n-chimerin, is a protein which in humans is encoded by the CHN1 gene.

Chimerin 1 is a GTPase activating protein specific for RAC GTP-binding proteins. It is expressed primarily in the brain and may be involved in signal transduction.

This gene encodes GTPase-activating protein for p21-rac and a phorbol ester receptor. It plays an important role in ocular motor axon pathfinding.

Function

CHN1 is a three-domain protein with the N-terminal SH2 domain, the C-terminal RhoGAP domain and the central C1 domain similar to protein kinase C. When lipid diacylglycerol (DAG) binds to the C1 domain, CHN1 is transferred to the plasma membrane and negatively regulates Rho-family small GTPases RAC1 and CDC42, thus causing the morphological change of axons by pruning the ends of axon dendrites.

Mutational analysis suggests that un-overlapping residues of the RhoGAP domain are involved in RAC1-binding and the RAC1-GAP activity. Regulation of the RhoGAP activity of CHN1 by phorbol esters, natural compounds mimic of the lipid second messenger DAG, presents a possible way of designing agents for therapeutics.

Clinical significance

Heterozygous missense mutations in this gene cause Duane's retraction syndrome 2 (DURS2).

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000128656 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000056486 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "RCSB Protein Data Bank - Structure Summary for 3CXL - Crystal structure of human chimerin 1 (CHN1)".
↑ Hall C, Monfries C, Smith P, Lim HH, Kozma R, Ahmed S, Vanniasingham V, Leung T, Lim L (January 1990). "Novel human brain cDNA encoding a 34,000 Mr protein n-chimaerin, related to both the regulatory domain of protein kinase C and BCR, the product of the breakpoint cluster region gene". J. Mol. Biol. 211 (1): 11–6. doi:10.1016/0022-2836(90)90006-8. PMID 2299665.
↑ Qi RZ, Ching YP, Kung HF, Wang JH (March 2004). "Alpha-chimaerin exists in a functional complex with the Cdk5 kinase in brain". FEBS Lett. 561 (1–3): 177–80. Bibcode:2004FEBSL.561..177Q. doi:10.1016/S0014-5793(04)00174-7. PMID 15013773. S2CID 39605825.
↑ Buttery P, Beg AA, Chih B, Broder A, Mason CA, Scheiffele P (February 2006). "The diacylglycerol-binding protein α1-chimaerin regulates dendritic morphology". Proc. Natl. Acad. Sci. U.S.A. 103 (6): 1924–9. Bibcode:2006PNAS..103.1924B. doi:10.1073/pnas.0510655103. PMC 1413663. PMID 16446429.
↑ Kozma R, Ahmed S, Best A, Lim L (September 1996). "The GTPase-activating protein n-chimaerin cooperates with Rac1 and Cdc42Hs to induce the formation of lamellipodia and filopodia". Mol. Cell. Biol. 16 (9): 5069–80. doi:10.1128/mcb.16.9.5069. PMC 231508. PMID 8756665.
↑ Kazanietz MG (December 2005). "Targeting protein kinase C and "non-kinase" phorbol ester receptors: emerging concepts and therapeutic implications". Biochim. Biophys. Acta. 1754 (1–2): 296–304. doi:10.1016/j.bbapap.2005.07.034. PMID 16202672.
↑ Miyake N, Chilton J, Psatha M, Cheng L, Andrews C, Chan WM, Law K, Crosier M, Lindsay S, Cheung M, Allen J, Gutowski NJ, Ellard S, Young E, Iannaccone A, Appukuttan B, Stout JT, Christiansen S, Ciccarelli ML, Baldi A, Campioni M, Zenteno JC, Davenport D, Mariani LE, Sahin M, Guthrie S, Engle EC (August 2008). "Human CHN1 mutations hyperactivate α2-chimaerin and cause Duane's retraction syndrome". Science. 321 (5890): 839–43. Bibcode:2008Sci...321..839M. doi:10.1126/science.1156121. PMC 2593867. PMID 18653847.

External links

GeneReviews/NCBI/NIH/UW entry on Duane syndrome
Chimerin+1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on human chromosome 2 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000128656 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000056486 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[urlRCSB_Protein_Data_Bank_-_Structure_Summary_for_3CXL_-_Crystal_structure_of_human_chimerin_1_(CHN1)-5] "RCSB Protein Data Bank - Structure Summary for 3CXL - Crystal structure of human chimerin 1 (CHN1)".

[pmid2299665-6] Hall C, Monfries C, Smith P, Lim HH, Kozma R, Ahmed S, Vanniasingham V, Leung T, Lim L (January 1990). "Novel human brain cDNA encoding a 34,000 Mr protein n-chimaerin, related to both the regulatory domain of protein kinase C and BCR, the product of the breakpoint cluster region gene". J. Mol. Biol. 211 (1): 11–6. doi:10.1016/0022-2836(90)90006-8. PMID 2299665.

[pmid15013773-7] Qi RZ, Ching YP, Kung HF, Wang JH (March 2004). "Alpha-chimaerin exists in a functional complex with the Cdk5 kinase in brain". FEBS Lett. 561 (1–3): 177–80. Bibcode:2004FEBSL.561..177Q. doi:10.1016/S0014-5793(04)00174-7. PMID 15013773. S2CID 39605825.

[pmid16446429-8] Buttery P, Beg AA, Chih B, Broder A, Mason CA, Scheiffele P (February 2006). "The diacylglycerol-binding protein α1-chimaerin regulates dendritic morphology". Proc. Natl. Acad. Sci. U.S.A. 103 (6): 1924–9. Bibcode:2006PNAS..103.1924B. doi:10.1073/pnas.0510655103. PMC 1413663. PMID 16446429.

[pmid8756665-9] Kozma R, Ahmed S, Best A, Lim L (September 1996). "The GTPase-activating protein n-chimaerin cooperates with Rac1 and Cdc42Hs to induce the formation of lamellipodia and filopodia". Mol. Cell. Biol. 16 (9): 5069–80. doi:10.1128/mcb.16.9.5069. PMC 231508. PMID 8756665.

[pmid16202672-10] Kazanietz MG (December 2005). "Targeting protein kinase C and "non-kinase" phorbol ester receptors: emerging concepts and therapeutic implications". Biochim. Biophys. Acta. 1754 (1–2): 296–304. doi:10.1016/j.bbapap.2005.07.034. PMID 16202672.

[pmid18653847-11] Miyake N, Chilton J, Psatha M, Cheng L, Andrews C, Chan WM, Law K, Crosier M, Lindsay S, Cheung M, Allen J, Gutowski NJ, Ellard S, Young E, Iannaccone A, Appukuttan B, Stout JT, Christiansen S, Ciccarelli ML, Baldi A, Campioni M, Zenteno JC, Davenport D, Mariani LE, Sahin M, Guthrie S, Engle EC (August 2008). "Human CHN1 mutations hyperactivate α2-chimaerin and cause Duane's retraction syndrome". Science. 321 (5890): 839–43. Bibcode:2008Sci...321..839M. doi:10.1126/science.1156121. PMC 2593867. PMID 18653847.